Steroid receptor coactivator 2: an essential coregulator of progestin-induced uterine and mammary morphogenesis.

A. Mukherjee, P. Amato, D. Craig-Allred, F. J. DeMayo, B. W. O'Malley, J. P. Lydon

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

The importance of the progesterone receptor (PR) in transducing the progestin signal is firmly established in female reproductive and mammary gland biology; however, the coregulators preferentially recruited by PR in these systems have yet to be comprehensively investigated. Using an innovative genetic approach, which ablates gene function specifically in murine cell-lineages that express PR, steroid receptor coactivator 2 (SRC-2, also known as TIF-2 or GRIP-1) was shown to exert potent coregulator properties in progestin-dependent responses in the uterus and mammary gland. Uterine cells positive for PR (but devoid of SRC-2) led to an early block in embryo implantation, a phenotype not shared by knockouts for SRC-1 or SRC-3. In the case of the mammary gland, progestin-dependent branching morphogenesis and alveologenesis failed to occur in the absence of SRC-2, thereby establishing a critical coactivator role for SRC-2 in cellular proliferative programs initiated by progestins in this tissue. Importantly, the recent detection of SRC-2 in both human endometrium and breast suggests that this coregulator may provide a new clinical target for the future management of female reproductive health and/or breast cancer.

Original languageEnglish (US)
Pages (from-to)55-76
Number of pages22
JournalErnst Schering Foundation symposium proceedings
Issue number1
StatePublished - 2007
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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